Somatic delusions frequently occur in psychotic patients where they accrete more polythematic-like explanations, but they can also occur outside a network of other delusional beliefs, remarkably like the syndromes observed in neurological patients with imageable lesions in their right frontal lobe 11. It is for this reason that among the illnesses discussed here, dementia in AD is particularly interesting, because it is primarily a cholinergic disturbance 10. Anatomically, aberrant salience is mediated by midbrain dopaminergic projections to mesocorticolimbic areas 8, 9. In psychosis, salience appears not as a result of exogenous stimuli but rather stems from “an endogenously driven assignment of novelty and salience to stimuli” 8, 9. In health, dopamine (DA) neurotransmission mediates the motivational salience of environmental rewards. In particular, delusions occur in Alzheimer, Parkinson, and Huntington diseases (HDs), delirium, post-ictal states and bipolar disorder among others, different illnesses presenting with a differential predominance of delusional themes and duration of symptoms, and sometimes correlating with other symptoms such as perceptual disturbances 7.ĭysfunction of the dopaminergic system has traditionally been assigned the central role in the pathogenesis of psychotic symptoms 8. Typically, research on delusions has focused on the wide palette of schizophrenia spectrum disorders, but the basic mechanisms of delusion formation are shared among multiple disease states 6. Delusions only rarely occur in isolation from other psychotic symptoms 4, although this does occur in the so-called delusional disorder 2, 5. The classical definition of delusions as false beliefs, and hallucinations as perceptions without corresponding external stimuli, have been criticized as oversimplistic 3. Capgras, Fregoli, reduplication, or arguably, neglect syndromes, in which the patient is often remarkably disinterested in connecting to other beliefs and experiences-and the themed delusions named previously.īoth hallucinations and delusions are present in many neuropsychiatric illnesses. Furthermore, it has long been recognized that there is a difference between somatic delusions-e.g. That these themes are constant across cultures suggests an underlying biology. Another important aspect of delusional belief is its specificity: delusions tend to cluster into certain themes, such as persecutory, grandiose, erotomanic, or somatic. This definition highlights the central differentiating aspects of delusions, which allow us to identify them in the clinic and distinguish them from other kinds of aberrant beliefs, including non-pathological ones: in particular, the fixedness of the belief (conviction) and cultural non-appropriateness (idiosyncrasy). Of note, the new edition of DSM captured an important nuance, namely that it is the dysfunctional process of belief, rather than its content necessarily being false, which is significant. We conclude by pointing out the need for further research both at the clinical and translational levels.ĭSM-5 1, 2 defines delusions as fixed beliefs that are not amenable to change in light of conflicting evidence. This hypothesis is consistent with our current knowledge about the mechanism of action of cholinergic drugs and with our abstract models of basic cognitive mechanisms at the molecular and circuit levels. Striosomes are proposed to play a central role in the formation of delusions. Beginning with what we know about the emergence of delusions in these illnesses, we advance a hypothesis of cholinergic disturbance in the dorsal striatum where nicotinic receptors are operative. Here we review the role of cholinergic neurotransmission in delusions, with a focus on nicotinic receptors, which are known to play a part in some illnesses where these symptoms appear, including delirium, schizophrenia spectrum disorders, bipolar disorder, Parkinson, Huntington, and Alzheimer diseases. Although scientific progress on this complex topic has been challenging, some recent advances focus on dysfunction in neural circuits, specifically in those involving dopaminergic and glutamatergic neurotransmission. Delusions are a difficult-to-treat and intellectually fascinating aspect of many psychiatric illnesses.
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